Phytochrome (Pr) is a linear tetrapyrrole derivative that serves as the on-off switch in photomorphogenesis. Its mode of action remains unclear. This study takes advantage of the reversible cleavage of the chromophore from its protein complex, which affords phytochromobilin (P0B) and apoprotein N-C. Synthetic P0B labeled specifically at C15-C16 will be incorporated into recombinant N-C to afford 13C-substituted native Pr. Raman spectroscopy will then be used to probe configuration and conformation changes during photoactivation to Pfr. We have recently completed a practical enantioselective synthesis of P0B methyl ester. New methodology will be applied to the synthesis and study of biologically active tetrapyrroles of the chlorin bacteriochlorin and corrin class. In nature, these macrocylces serve important functions as co-factors, vitamins, and light absorbing pigments. They also have significant medical potential. For example, certain members of this class show promise in photodynamic therapy, in which selectively absorbed pigments destroy cancerous tissue by photostimulated production of singlet oxygen. Currently there are few methods available for the stereo- and enantioselective preparation of these compounds. An iterative synthesis is under development which offers excellent control over both relative and absolute stereochemistry. Preliminary results are very promising.